Ethanol induced impairment of in vitro cerebral protein and RNA synthesis has been reported. Presently we examined ethanol effects under chronic conditions and following the development of physical dependence and withdrawal on brain macromolecular metabolism. In addition, ethanol effects were studied on properties of neural cells grown in culture. Our studies on protein synthesis revealed that under the above conditions of ethanol treatment, ribosomes from cerebral hemispheres and the cerebellar region of the brain had decreased ability for in vitro protein synthesis. Furthermore, although ethanol had no effect on the dissociation properties of ribosomes, it had adverse effects on the reassociation process as evidenced by the decreased in vitro synthesis of (14C)-polyphenylalanine. Studies on RNA metabolism showed distinct enzymatic activities for RNA and poly (A) synthesis by the nuclear soluble and particulate fractions with the ethanol group demonstrating reduced activity. Furthermore, the migration and association of a rapidly labeled RNA to ribosomes in the cytoplasm from (3H) labeled nuclei was decreased under chronic conditions. Using neural cell lines, ethanol decreased the acute transport of leucine, but not of aminoisobutyric acid (AIB). Currently we are examining in depth the ethanol effects on the reactions of protein biosynthesis.